A variety of biomedical materials, plastics, metals, and acrylics are implanted into patients in many forms and in large numbers. A distrubingly large proportion of patients with surgical biomaterials (e.g., 1-11% of all prosthetic hip devices, or 15,000 to 30,000 patients per year) become chronically infected. These infections respond notoriously poorly to antibiotic therapy and may necessitate the removal of the biomaterial with unfortunate sequelae. Recently developed insights in microbiology have shown that surface adhesion is the first step of the pathogenic process, suggesting that bacteria may colonize an inert surface within the body if introduced during implantation of the device or if carried to the area by transient bacteremia. We know that bacteria adhere to inert surfaces (e.g., pipes in cooling towers, rocks in alpine streams and dental enamel) by means of exopolysaccharide fibers, the glycocalyx. The discrimination of these processes has obvious importance. We propose to continue to recover these adherent bacteria from actual cases of infected surgical biomedical implants and to establish them as adherent populations on a variety of metal and plastic surfaces in vitro. Our preliminary direct observation of material from infected internal fixation devices has demonstrated adherent bacteria surrounded by extracellular fibers, and we have isolated these bacteria and demonstrated their adhesion to metal and plastic surfaces by means of their surface polysaccharide. We propose to study the effect of this mode of growth on resistance to clearance by macrophages and on resistance to antibiotics. By developing an understanding of the bacterial colonization of a wide variety of surgical materials, we seek to select materials and finishing processes that minimize bacterial adhesion and maximize clearance by macrophages. By studying the chemistry of the bacterial exopolysaccharide and its role in antibiotic resistance, we seek to optimize antimicrobial therapy.